Nosocomial infections continue to be significant causes of morbidity, mortality, and added costs in the health care setting. Half of all life-threatening nosocomial bloodstream infections and pneumonias occur in intensive care units (ICUs), despite ICUs representing only 15 to 20% of all hospital beds. Thus an efficient focus for prevention and control of life-threatening health care-associated infections should be in ICUs. Further, growing antibiotic resistance complicates the therapy of serious infections. Meticulous infection control practice with continued attention to hand hygiene is of paramount importance. Strict adherence to evidence-based catheter insertion and maintenance policies reduces nosocomial bloodstream infections. Evidence-based prevention strategies for ventilator-associated pneumonia, including management of respiratory equipment according to published guidelines and maintaining backrest elevation at 30 to 45 degrees, are effective. For greatest risk reduction, multifaceted programs ensuring maximal adherence with evidence-based infection control guidelines are needed.